The Essential and Enigmatic Role of ABC Transporters in Bt Resistance of Noctuids and Other Insect Pests of Agriculture

SIMPLE SUMMARY: The insect family, Noctuidae, contains some of the most damaging pests of agriculture, including bollworms, budworms, and armyworms. Transgenic cotton and maize expressing Cry-type insecticidal proteins from Bacillus thuringiensis (Bt) are protected from such pests and greatly reduce the need for chemical insecticides. However, evolution of Bt resistance in the insects threatens the sustainability of this environmentally beneficial pest control strategy. Understanding the interaction between Bt toxins and their targets in the insect midgut is necessary to evaluate the risk of resistance evolution. ABC transporters, which in eukaryotes typically expel small molecules from cells, have recently been proposed as a target for the pore-forming Cry toxins. Here we review the literature surrounding this hypothesis in noctuids and other insects. Appreciation of the critical role of ABC transporters will be useful in discovering counterstrategies to resistance, which is already evolving in some field populations of noctuids and other insects. ABSTRACT: In the last ten years, ABC transporters have emerged as unexpected yet significant contributors to pest resistance to insecticidal pore-forming proteins from Bacillus thuringiensis (Bt). Evidence includes the presence of mutations in resistant insects, heterologous expression to probe interactions with the three-domain Cry toxins, and CRISPR/Cas9 knockouts. Yet the mechanisms by which ABC transporters facilitate pore formation remain obscure. The three major classes of Cry toxins used in agriculture have been found to target the three major classes of ABC transporters, which requires a mechanistic explanation. Many other families of bacterial pore-forming toxins exhibit conformational changes in their mode of action, which are not yet described for the Cry toxins. Three-dimensional structures of the relevant ABC transporters, the multimeric pore in the membrane, and other proteins that assist in the process are required to test the hypothesis that the ATP-switch mechanism provides a motive force that drives Cry toxins into the membrane. Knowledge of the mechanism of pore insertion will be required to combat the resistance that is now evolving in field populations of insects, including noctuids.